The aim is to determine the molecular structure of the adenovirus capsid by X-ray crystallographic analysis of the individual capsid proteins hexon and penton. The structure of type 2 hexon, the major coat protein (MW 3 x 115,000), has already been determined to low resolution and work is in progress at 2.9 A resolution. This analysis will define the folding of the 1050 amino acid chain and correlate it with the chemical sequence. A detailed molecular model will then be constructed by using a computer graphics model-building system followed by least-squares of structure refinement, after extension of the data to 2 A resolution. The penton structure, if the vertex protein can be crystallized, will complete the view of the viral shell. The adenovirus capsid should serve as a simple model for study of the protein interactions giving the specific recognition required for rapid and unique biological assembly. The hexon-hexon interactions in the capsid, already coarsely defined by our low resolution hexon models, will be studied at the level of amino-acid side-chain interactions by using the refined molecular structure. The structure of the immunologically distinct type 5 hexon, known to crystallize isomorphously, will also be determined. Identification of the structural basis for the immunological differences between types 2 and 5 will then be possible, and a comparison of these differences for further types will show how the adenovirus coat has differentiated. Hexon will thus not only be the first example of a human viral protein seen in detail, but will also provide an example for which immunological differences can be defined exactly. Such correlations may be of particular significance since hexon may be used as a vaccine in place of the oncogenic complete virus.